arXiv:2502.00694cs.LGcs.AI2025-02被引 5

用大模型预测抗体对流感病毒的结合与阻断能力,加速药物研发。

Leveraging Large Language Models to Predict Antibody Biological Activity Against Influenza A Hemagglutinin

  • 基于抗体序列,用AI模型预测其与流感血凝素的结合和阻断活性。
  • 对已见抗原的预测AUROC超0.91,对新抗原也达0.9,新抗体预测为0.73。
  • 适合药物研发人员快速筛选候选抗体,尤其在数据多样时效果更佳。

单克隆抗体(mAbs)是治疗自身免疫病、传染病和癌症的主流FDA批准疗法,但其发现与开发过程耗时且昂贵。机器学习与人工智能的进步为抗体发现与优化带来新可能。特别是能预测抗体生物活性的模型,可实现结合与功能性质的虚拟评估,从而在昂贵且耗时的实验前优先筛选高成功率候选抗体。本文采用MAMMAL框架,仅利用序列信息构建模型,预测抗体对甲型流感血凝素(HA)的结合与受体阻断活性。在多种数据划分条件下测试,模型对已见HA的预测AUROC ≥0.91,对未见HA的预测达到0.9;对全新抗体的预测AUROC为0.73,在严格限制相似性条件下降至0.63–0.66。结果表明,AI基础模型有望通过减少实验依赖,提升抗体候选物的筛选效率。同时强调,多样化且全面的抗体数据集对提升模型泛化能力至关重要,尤其在新抗体开发中。

原文摘要 · Abstract (English)

Monoclonal antibodies (mAbs) represent one of the most prevalent FDA-approved modalities for treating autoimmune diseases, infectious diseases, and cancers. However, discovery and development of therapeutic antibodies remains a time-consuming and expensive process. Recent advancements in machine learning (ML) and artificial intelligence (AI) have shown significant promise in revolutionizing antibody discovery and optimization. In particular, models that predict antibody biological activity enable in-silico evaluation of binding and functional properties; such models can prioritize antibodies with the highest likelihoods of success in costly and time-intensive laboratory testing procedures. We here explore an AI model for predicting the binding and receptor blocking activity of antibodies against influenza A hemagglutinin (HA) antigens. Our present model is developed with the MAMMAL framework for biologics discovery to predict antibody-antigen interactions using only sequence information. To evaluate the model's performance, we tested it under various data split conditions to mimic real-world scenarios. Our models achieved an AUROC $\geq$ 0.91 for predicting the activity of existing antibodies against seen HAs and an AUROC of 0.9 for unseen HAs. For novel antibody activity prediction, the AUROC was 0.73, which further declined to 0.63-0.66 under stringent constraints on similarity to existing antibodies. These results demonstrate the potential of AI foundation models to transform antibody design by reducing dependence on extensive laboratory testing and enabling more efficient prioritization of antibody candidates. Moreover, our findings emphasize the critical importance of diverse and comprehensive antibody datasets to improve the generalization of prediction models, particularly for novel antibody development.

抗体设计AI制药流感研究大模型

Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。